Classifications

• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K31/00—Medicinal preparations containing organic active ingredients
  • A61K31/045—Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates
  • A61K31/05—Phenols
  • A61K31/055—Phenols the aromatic ring being substituted by halogen
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P25/00—Drugs for disorders of the nervous system
  • A61P25/08—Antiepileptics; Anticonvulsants
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P25/00—Drugs for disorders of the nervous system
  • A61P25/24—Antidepressants
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P25/00—Drugs for disorders of the nervous system
  • A61P25/26—Psychostimulants, e.g. nicotine, cocaine
• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
  • C07C249/00—Preparation of compounds containing nitrogen atoms doubly-bound to a carbon skeleton
  • C07C249/02—Preparation of compounds containing nitrogen atoms doubly-bound to a carbon skeleton of compounds containing imino groups
• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
  • C07C251/00—Compounds containing nitrogen atoms doubly-bound to a carbon skeleton
  • C07C251/02—Compounds containing nitrogen atoms doubly-bound to a carbon skeleton containing imino groups
  • C07C251/24—Compounds containing nitrogen atoms doubly-bound to a carbon skeleton containing imino groups having carbon atoms of imino groups bound to carbon atoms of six-membered aromatic rings

Definitions

• the present invention relates to substituted diphenylazomethines, their preparation and their therapeutic use.
• the diphenylazomethines according to the invention correspond to the formula (I): ##STR2## in which R represents --(CH 2 ) 4 OH, --(CH 2 ) 2 --CHOH--CH 3 , --CH 2 --CHOH--C 2 H 5 , --CH 2 --CHOH--CH 2 --COOH, --CH 2 --CHOH--CH 2 CONH 2 , --CH 2 --CH 2 --CHOH--CH 2 OH or CH 2 --CHOH--COOH.
• Those compounds of formula (I) which contain an asymmetric carbon may exist in the racemic form or in the form of their enantiomers.
• the diphenylazomethines of formula (I) are prepared by a process which comprises reacting a benzophenone of the formula ##STR3## with a compound of the formula H 2 N--R, if appropriate in the optically active enantiomer form.
• the reaction can be carried out at a temperature from 30° to 120° C. in a solvent such as ether, methanol, ethanol or toluene.
• reaction mixture is brought to the boiling point and the solvent is evaporated.
• residue is purified by chromatography on a silica column, the column being eluted with a mixture of chloroform/ethyl acetate.
• fractions containing the intended product are combined and evaporated to dryness.
• An oil is obtained, which is crystallised in petroleum ether.
• the mixture is evaporated to dryness, the residue is partitioned between water and methylene chloride, the organic phase is decanted, dried over MgSO 4 and filtered and the filtrate is evaporated to dryness.
• the product is purified on a silica column with ethyl acetate as the eluant and the product is recrystallised from pentane, after treatment with vegetable charcoal.
• the enantiomers of this compound were prepared in the same manner by a reaction between (2-chlorophenyl)-(5-chloro-2-hydroxyphenyl)-methanone and the enantiomers of 4-aminobutan-2-ol.
• Diphenylazomethines according to the invention have been subjected to pharmacological tests demonstrating their action on the central nervous system.
• the acute toxicity was determined on mice by intraperitoneal administration.
• the LD 50 (50% lethal dose) varies from 200 to 600 mg/kg.
• L-5-hydroxytrlyptophan L-5-HTP
• mice (CDI males, Charles River France; 18-22 g body weight) received increasing doses of the products to be studied, or the solvent, subcutaneously, together with L-5-HTP in a dose of 250 mg/kg. 45 minutes after this injection of L-5-HTP, the number of head twitches of each mouse is counted for one minute.
• the average number of head twitches and the percentage variation relative to a control group are calculated.
• the AD 50 (50% active dose or dose which reduces the average number of head twitches by 50%) is determined from the dose-effect curve by the graphical method of Miller and Tainter (1944).
• the AD 50 on intraperitoneal administration of the compounds according to the invention varies from 20 to 40 mg/kg.
• the anticonvulsive activity of the compound was demonstrated by antagonism to the mortality induced by bicuculline in mice.
• Bicuculline is a relatively selective blocker of post-synaptic GABA-ergic receptors and its convulsive and lethal effects are antagonised by compounds which increase the level of cerebral GABA or have a GABA-mimetic activity.
• AD 50 50% active dose
• the AD 50 on intraperitoneal administration of the compounds according to the invention varies from 20 to 100 mg/kg.
• the compounds according to the invention are active as antidepressants and anticonvulsants and also have anxiolytic, analgesic and antiinflammatory properties. They can be used in human and veterinary therapy for the treatment of various diseases of the central nervous system, for example for the treatment of depressions, psychoses and some neurological diseases, such as epilepsy, spasticity and diskinesia.
• the invention accordingly relates to all pharmaceutical compositions containing the compounds (I) as active principles together with any excipients suitable for their administration, in particular oral (tablets, coated tablets, gelatin capsules, capsules, cachets and solutions or suspensions for oral use) or parenteral administration.
• the daily posology may be from 250 to 5,000 mg.

Landscapes

• Chemical & Material Sciences (AREA)
• Organic Chemistry (AREA)
• Health & Medical Sciences (AREA)
• Veterinary Medicine (AREA)
• Medicinal Chemistry (AREA)
• Pharmacology & Pharmacy (AREA)
• Life Sciences & Earth Sciences (AREA)
• Animal Behavior & Ethology (AREA)
• General Health & Medical Sciences (AREA)
• Public Health (AREA)
• Engineering & Computer Science (AREA)
• Chemical Kinetics & Catalysis (AREA)
• Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
• Bioinformatics & Cheminformatics (AREA)
• Biomedical Technology (AREA)
• Neurology (AREA)
• Neurosurgery (AREA)
• General Chemical & Material Sciences (AREA)
• Psychiatry (AREA)
• Epidemiology (AREA)
• Pain & Pain Management (AREA)
• Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
• Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
• Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
• Nitrogen- Or Sulfur-Containing Heterocyclic Ring Compounds With Rings Of Six Or More Members (AREA)
• Thiazole And Isothizaole Compounds (AREA)

Applications Claiming Priority (2)

Publications (1)

Family

ID=9287835

Family Applications (1)

Country Status (23)

Cited By (3)

Citations (5)

Family Cites Families (1)

• 1983
  • 1983-04-14 FR FR8306081A patent/FR2544308B1/fr not_active Expired
• 1984
  • 1984-04-13 LU LU85312A patent/LU85312A1/fr unknown
  • 1984-04-13 IL IL71539A patent/IL71539A0/xx unknown
  • 1984-04-13 IT IT20527/84A patent/IT1176041B/it active
  • 1984-04-13 US US06/599,799 patent/US4564636A/en not_active Expired - Fee Related
  • 1984-04-13 ZA ZA842799A patent/ZA842799B/xx unknown
  • 1984-04-13 PT PT78428A patent/PT78428B/pt not_active IP Right Cessation
  • 1984-04-13 DE DE19843414050 patent/DE3414050A1/de not_active Withdrawn
  • 1984-04-13 SE SE8402081A patent/SE8402081L/xx not_active Application Discontinuation
  • 1984-04-13 CH CH1877/84A patent/CH659649A5/fr not_active IP Right Cessation
  • 1984-04-13 FI FI841483A patent/FI841483A7/fi not_active Application Discontinuation
  • 1984-04-13 NL NL8401190A patent/NL8401190A/nl not_active Application Discontinuation
  • 1984-04-13 DK DK191584A patent/DK191584A/da not_active Application Discontinuation
  • 1984-04-13 HU HU841455A patent/HU191556B/hu not_active IP Right Cessation
  • 1984-04-13 BE BE0/212764A patent/BE899422A/fr not_active IP Right Cessation
  • 1984-04-13 CA CA000452021A patent/CA1212957A/en not_active Expired
  • 1984-04-13 NO NO841485A patent/NO154696C/no unknown
  • 1984-04-13 ES ES531586A patent/ES8501737A1/es not_active Expired
  • 1984-04-13 NZ NZ207841A patent/NZ207841A/en unknown
  • 1984-04-13 GR GR74420A patent/GR79888B/el unknown
  • 1984-04-13 JP JP59075678A patent/JPS59199664A/ja active Pending
  • 1984-04-13 AU AU26822/84A patent/AU560988B2/en not_active Ceased
  • 1984-04-13 GB GB08409685A patent/GB2138422B/en not_active Expired

Patent Citations (6)

Non-Patent Citations (2)

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